Control mechanisms in cells that participate in immunologic inflammation will be studied with particular reference to the role of cyclic AMP and cyclic GMP in lymphocyte activation, histamine release, phagocytosis and chemotaxis: 1) Highly purified preparations of cells (human and rat lymphocytes, rat mast cells and basophilic leukemia cells, human polymorphonuclear leukocytes and guinea pig and human alveolar macrophages) will be obtained. 2) Biochemical measurements will be made before, during and after exposure to a variety of immunologic and nonimmunologic stimuli. Cells will be studied for changes in cyclic AMP and cyclic GMP concentrations or distribution comparing the kinetics of any alterations observed with those of the immunological relevant response. 3) Pharmacologic or biological agents which enhance or inhibit cell activation will be studied for effects on cyclic nucleotide metabolism. 4) The enzymes that synthesize and degrade cAMP or modulate its action (adenylate and guanylate cyclase, cyclic nucleotide phosphodiesterase, cyclic nucleotide dependent protein kinases) will be purified and characterized and the mechanism by which extracellular stimuli alter cyclic nucleotide metabolism defined. 5) Highly purified subcellular fractions will be obtained and possible mechanisms of local cyclic nucleotide action studied. BIBLIOGRAPHIC REFERENCES: Atkinson, J.P. and Parker, C.W.: Autoimmunity associated with skin in experimental systems and in nonbullous human diseases. In Textbook of Immunopathology. P.A. Miescher, Editor, Grune and Stratton, 1975. Parker, C.W.: Possible mechanisms of lymphocyte activation. In Immune Recognition, edited by A.S. Rosenthal, Academic Press , 1975.